Avtor/Urednik     Ačimovič, Jure; Fink, Martina; Pompon, Denis; Bjorkhem, Ingemar; Hirayama, Jun; Sassone-Corsi, Paolo; Goličnik, Marko; Rozman, Damjana
Naslov     CREM modulates the circadian expression of CYP51, HMGCR, and cholesterogenesis in the liver
Tip     članek
Vir     Biochem Biophys Res Commun
Vol. in št.     Letnik 376, št. 1
Leto izdaje     2008
Obseg     str. 206-10
Jezik     eng
Abstrakt     We show for the first time that isoforms of the cAMP response element modulator Crem, regulate the circadian expression of Cyp51 and other cholesterogenic genes in the mouse liver. In the wild type mice the expression of Cyp51, Hmgs, Fpps, and Sqs is minimal between CT12 and CT16 and peaks between CT20 and CT24. Cyp51, Fpps, and Sqs lost the circadian behavior in Crem-/- livers while Hmgcr is phase advanced from CT20 to CT12. This coincides with a phase advance of lathosterol/cholesterol ratio, as detected by GC-MS. Overexpression of CREMtau and ICER has little effect on the Hmgcr proximal promoter while they influence expression from the CYP51 promoter. Our data indicate that Crem-dependent regulation of Cyp51 in the liver results in circadian expression of this gene. We propose that cAMP signaling might generally be involved in the circadian regulation of cholesterol synthesis on the periphery.
Deskriptorji     LIVER
CHOLESTEROL
CYTOCHROME P-450
CYCLIC AMP
GENE EXPRESSION
MICE
CIRCADIAN RHYTHM
PROMOTER REGIONS (GENETICS)